Abstract
Down syndrome (DS) individuals develop several neuropathological hallmarks seen in Alzheimer's disease, including cognitive decline and the early loss of cholinergic markers in the basal forebrain. These deficits are replicated in the Ts65Dn mouse, which contains a partial trisomy of murine chromosome 16, the orthologous genetic segment to human chromosome 21. Oxidative stress levels are elevated early in DS, and may contribute to the neurodegeneration seen in these individuals. We evaluated oxidative stress in Ts65Dn mice, and assessed the efficacy of long-term antioxidant supplementation on memory and basal forebrain pathology. We report that oxidative stress was elevated in the adult Ts65Dn brain, and that supplementation with the antioxidant vitamin E effectively reduced these markers. Also, Ts65Dn mice receiving vitamin E exhibited improved performance on a spatial working memory task and showed an attenuation of cholinergic neuron pathology in the basal forebrain. This study provides evidence that vitamin E delays onset of cognitive and morphological abnormalities in a mouse model of DS, and may represent a safe and effective treatment early in the progression of DS neuropathology.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Acetylcholine / metabolism
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Age Factors
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Amyloid beta-Protein Precursor / metabolism
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Analysis of Variance
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Animals
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Calbindins
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Choline O-Acetyltransferase / metabolism
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Chromosomes, Mammalian
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Disease Models, Animal
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Down Syndrome / complications*
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Down Syndrome / genetics
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Gene Expression Regulation / genetics
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Gene Expression Regulation / physiology
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Male
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Maze Learning / drug effects
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Maze Learning / physiology
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Memory Disorders / drug therapy*
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Memory Disorders / etiology
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Memory, Short-Term / drug effects
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Memory, Short-Term / physiology
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Mice
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Mice, Inbred C3H
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Mice, Neurologic Mutants
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Nerve Degeneration / drug therapy*
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Nerve Degeneration / etiology
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Neuroprotective Agents / administration & dosage*
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Prosencephalon / pathology
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Psychomotor Performance / drug effects
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Psychomotor Performance / physiology
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Reactive Oxygen Species / metabolism
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S100 Calcium Binding Protein G / metabolism
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Tocopherols / administration & dosage*
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Trisomy
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Vitamins / administration & dosage*
Substances
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Amyloid beta-Protein Precursor
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Calbindins
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Neuroprotective Agents
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Reactive Oxygen Species
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S100 Calcium Binding Protein G
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Vitamins
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Choline O-Acetyltransferase
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Acetylcholine
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Tocopherols